This is an open-label, multinational, randomized, multicenter trial designed to compare pegylated liposomal doxorubicin with capecitabine as first line chemotherapy of metastatic breast cancer. The primary objective of the study is to compare the time to disease progression, although overall response rates, overall survival, quality of life, time to treatment failure, and safety and tolerability will also be assessed.

Condition	Intervention	Phase
Breast Cancer	Drug: pegylated liposomal doxorubicin  Drug: capecitabine	Phase IV

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Female

Criteria

Inclusion Criteria:

• Patients must be female.
• Patients must have metastatic disease of a cytological or histological confirmed breast cancer.
• Patients must be 18 years or older.
• Patients should have evaluable disease (at least uni-dimensionally measurable lesion according to the RECIST criteria in at least one site that has not been irradiated), however, patients who only have non-measurable/evaluable disease are not excluded. Also patients with only bone metastasis are not excluded.
• Patients must have an ECOG 0-2.
• Patients must have a life expectancy of ≥3 months.
• Patients must be willing and able to complete study questionnaires.
• Patients must have adequate renal function as evidenced by serum creatinine ≤1.5 mg/dL, or a creatinine clearance of ≥45 mL/min (if serum creatinine is > 1.5 mg/dL but ≤ 1.8 mg/dL).
• Patients must have adequate bone marrow function as evidenced by leukocyte count greater than 3.5 g/L, hemoglobin ≥9.0 g/dL, and platelet count ≥100x10**9/L.
• Patients must have adequate liver function as evidenced by bilirubin of ≤1.5 times the upper limits of normal (ULN) and alkaline phosphatase ≤3 times, ULN unless related to liver metastasis.
• Patients must have serum electrolytes within normal limits.
• Patients must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study.

Exclusion Criteria:

• History of receiving prior therapy in the metastatic setting [Note: patients may have had hormonal therapy or chemotherapy in the adjuvant setting; patients may have received hormonal therapy in metastatic setting].
• Patients who are taking concomitant medications (except bisphosphonates) for metastatic disease, including hormonal therapy, radiation therapy, trastuzumab, or biologicals are also not permitted.
• History of treatment with capecitabine or pegylated liposomal doxorubicin in the adjuvant setting. [Note: Prior use of anthracyclines other than pegylated liposomal doxorubicin in the adjuvant setting does not exclude a patient, provided an initial cardial monitoring at more than 360 mg/sq m doxorubicin (or equivalents) and anthracycline treatment concluded greater than 6 months ago].
• Patients with anthracycline resistant disease are not permitted. Anthracycline resistance is defined as development of locally recurrent or metastatic disease while on adjuvant anthracycline therapy, or relapse less than 6 months after completion of anthracycline therapy.
• Evidence of primary or metastatic malignancy involving the central nervous system unless previously treated and asymptomatic for 3 months or greater.
• Patients with reduced liver functions (evidenced by bilirubin of above 1.5 times the upper limits of normal (ULN); alkaline phosphatase above 3 times ULN (except related to liver metastasis, in which case ≤5 x ULN).
• Dyspnea on exertion.
• History of cardiac disease, with New York Heart Association Class II or greater, or clinical evidence of congestive heart failure or myocardial infarct within less than six months or an left ventricular ejection fraction (LVEF) below 50%.
• Woman with childbearing potential with insufficient contraception [hormonal or intrauterine device (IUD) are regarded as sufficient] during the study period and the six months following the last study drug application.
• Existing pregnancy or lactation (note on pregnancy test).
• Existing doubts on ability and willingness of the subject for cooperation.
• Participation of the subject at a clinical study within the last 30 days.
• Participation of the subject in the same clinical study at an earlier date.
• Concomitant participation in another study than the one described here.
• Abuse of drugs, alcohol, or pharmaceuticals.

Please refer to this study by ClinicalTrials.gov identifier  NCT00266799

Study chairs or principal investigators

Nadia Harbeck, M.D.,  Principal Investigator,  Klinikum Rechts der Isar d. TU München   

Study ID Numbers:  P04445
Last Updated:  December 16, 2005
Record first received:  December 15, 2005
ClinicalTrials.gov Identifier:  NCT00266799
Health Authority: Germany: Federal Institute for Drugs and Medicinal Devices
ClinicalTrials.gov processed this record on 2006-01-10